The long term objectives of this research proposal are to achieve an understanding of the neurobiology of the novel neuropeptide, cortistatin. Neuropeptides are biological signaling molecules that modulate a wide range of physiological functions such as synaptic transmission, and are involved in many health related conditions including Alzheimer's disease, cognitive deficiencies and sleep disorders. The neuropeptide cortistatin was recently cloned and the aims of this proposal are to confirm that this neuropeptide is expressed in the brain, released as a neurotransmitter, binds to specific sites in the brain and through these receptors causes physiological responses. The proposed characterization of cortistatin will facilitate the isolation or identification of cortistatin specific receptors; a vital element in understanding the signaling mechanisms of this novel neuropeptide and in providing a target for medically relevant compounds to treat disease states and disorders of the nervous systems.